ࡱ>  '` VJbjbj{P{P B::H0000000D4t4t4t8ltvDD6X{nƀ(-$ Ͻ2222222$\8h:d30m@3006.VVVp002V2VVn'00CL{ 4tPX/ ,H6<6O(;V(;@C(;0Cc"Vccc33Xccc6P8D(%D8l]DD(%l]DDD000000 NOTE TO USERS This Quality Agreement template was developed by the Bulk Pharmaceutical Task Force (BPTF), an affiliate organization of the Society of Chemical Manufacturers and Affiliates (SOCMA), as a guide for drafting a Quality Agreement relating to the manufacture and release of substances regulated by the Food and Drug Administration The template is based on the collective experience of industry members, but is not intended to be exhaustive or inclusive of all pertinent requirements. The information herein is offered in good faith, but is provided WITHOUT ANY WARRANTIES, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. Users are cautioned that the information upon which this template is based is subject to change. The responsibility allocations in the template are largely defined by the fact that only one party is in a position to exercise the responsibility identified. To the extent that the responsibility is shown as shared or can be assigned to the other party, the template allocation represents the experience of the BPTF members as to common practice. Parties utilizing the template are free to allocated responsibility and notification timing in any manner that assures all regulatory obligations are met. SOCMA and BPTF do not endorse the products or processes of any particular manufacturer, and this template is not intended to provide specific advice, legal or otherwise. Following this template does not guarantee compliance with applicable laws, rules, and regulations. Users should consult with their legal and technical advisors and other sources. SOCMA, BPTF, and their members and agents do not assume any responsibility for a users compliance with applicable laws, rules and regulations, and disclaim any liabilities arising out of or relating to the use of this template or reliance on any information contained herein. Quality Agreement by and between Supplier Name:Address: and Client Name:Address: Table of Contents  TOC \o "1-3" \h \z \u  HYPERLINK \l "_Toc266168226" Suppliers & Clients Name. PAGEREF _Toc266168226 \h 5  HYPERLINK \l "_Toc266168227" Custom Manufacturers Quality Agreement Template PAGEREF _Toc266168227 \h 6  HYPERLINK \l "_Toc266168228" 1. Effective Date  PAGEREF _Toc266168228 \h 6  HYPERLINK \l "_Toc266168229" 2. Scope .. PAGEREF _Toc266168229 \h 6  HYPERLINK \l "_Toc266168230" 3. Other Agreement...................................................................................................... PAGEREF _Toc266168230 \h 6  HYPERLINK \l "_Toc266168231" 4. Amendments to Quality Agreement  PAGEREF _Toc266168231 \h 6  HYPERLINK \l "_Toc266168232" 5. Term of Quality Agreement  PAGEREF _Toc266168232 \h 7  HYPERLINK \l "_Toc266168233" 6. Use of Third-Parties.  PAGEREF _Toc266168233 \h 7  HYPERLINK \l "_Toc266168234" 7. Survival Clause..  PAGEREF _Toc266168234 \h 7  HYPERLINK \l "_Toc266168235" 8. Assignment..  PAGEREF _Toc266168235 \h 8  HYPERLINK \l "_Toc266168236" 9. Product Specifications  PAGEREF _Toc266168236 \h 8  HYPERLINK \l "_Toc266168237" 10. Shipping Under Quarantine  PAGEREF _Toc266168237 \h 8  HYPERLINK \l "_Toc266168238" 11. Resolution of Quality Issues  PAGEREF _Toc266168238 \h 8  HYPERLINK \l "_Toc266168239" 12. Debarment.  PAGEREF _Toc266168239 \h 9  HYPERLINK \l "_Toc266168240" 13. Choice of Law: Jurisdiction/Miscellaneous  PAGEREF _Toc266168240 \h 9  HYPERLINK \l "_Toc266168241" 14. Manufacturing and Testing Location(s)  PAGEREF _Toc266168241 \h 9  HYPERLINK \l "_Toc266168242" 15. Quality Responsibilities Table  PAGEREF _Toc266168242 \h 10  HYPERLINK \l "_Toc266168243" Compliance Requirements  PAGEREF _Toc266168243 \h 10  HYPERLINK \l "_Toc266168244" Right to Audit  PAGEREF _Toc266168244 \h 10  HYPERLINK \l "_Toc266168245" Regulatory Inspections and Exchanges  PAGEREF _Toc266168245 \h 11  HYPERLINK \l "_Toc266168246" Regulatory Filings and Regulatory Status*  PAGEREF _Toc266168246 \h 11  HYPERLINK \l "_Toc266168247" Complaints and Recalls  PAGEREF _Toc266168247 \h 12  HYPERLINK \l "_Toc266168248" Animal Derived Materials  PAGEREF _Toc266168248 \h 12  HYPERLINK \l "_Toc266168249" Validation/Qualification  PAGEREF _Toc266168249 \h 13  HYPERLINK \l "_Toc266168250" Documentation and Records  PAGEREF _Toc266168250 \h 13  HYPERLINK \l "_Toc266168251" Annual Product Reviews  PAGEREF _Toc266168251 \h 14  HYPERLINK \l "_Toc266168252" Change Control  PAGEREF _Toc266168252 \h 14  HYPERLINK \l "_Toc266168253" Deviations  PAGEREF _Toc266168253 \h 15  HYPERLINK \l "_Toc266168254" Reprocess and Batch Adjustments /Rework/Retest  PAGEREF _Toc266168254 \h 15  HYPERLINK \l "_Toc266168255" Production and In Process Controls, Packaging and Labeling  PAGEREF _Toc266168255 \h 15  HYPERLINK \l "_Toc266168256" Storage and Distribution  PAGEREF _Toc266168256 \h 16  HYPERLINK \l "_Toc266168257" Laboratory Controls  PAGEREF _Toc266168257 \h 16  HYPERLINK \l "_Toc266168258" Stability (must decide Client or Supplier or NA)* if supplied by Client, Client will provide all necessary information to the supplier.  PAGEREF _Toc266168258 \h 17  HYPERLINK \l "_Toc266168259" Recalls  PAGEREF _Toc266168259 \h 17  HYPERLINK \l "_Toc266168260" APPENDIX 1: Definition of Product . PAGEREF _Toc266168260 \h 18  HYPERLINK \l "_Toc266168261" APPENDIX 2: Contacts and Responsibilities. PAGEREF _Toc266168261 \h 19  HYPERLINK \l "_Toc266168262" APPENDIX 3: Product Specifications PAGEREF _Toc266168262 \h 20  HYPERLINK \l "_Toc266168263" APPENDIX 4: List of Approved Subcontractors PAGEREF _Toc266168263 \h 21  Suppliers & Clients Name Suppliers Name (Supplier) and Clients Name (Client) wish to define the individual responsibilities of the parties as to the quality aspects of manufacturing and release of Product as defined in Appendix 1 to ensure compliance with the approved Product application and/or Client requirements. In order to do so, this Quality Agreement (Quality Agreement) takes the form, in part, of a detailed listing of activities associated with manufacture, supply, production, analysis, and release of Product. Unless otherwise indicated, responsibility for each activity is assigned to either Client, Supplier, or is assigned to both Supplier and Client. In consideration of the parties agreement to perform the activities provided in this Quality Agreement and for other valuable consideration the receipt and sufficiency of which is hereby acknowledged, and intending to be legally bound, Supplier and Client agree as provided in this Quality Agreement as follows: ClientSupplier SignatureSignatureNameNameTitle Title Signed the ____ day of___________ in the year 20__Signed the ____ day of___________ in the year 20__ Custom Manufacturers Quality Agreement Template Effective Date The Effective Date of this Quality Agreement shall be the date of last signature (the Effective Date). Scope This Quality Agreement outlines the responsibilities of Supplier and Client with respect to the quality assurance of the Product manufactured and/or supplied by Supplier for Client. Other Agreement This Quality Agreement is in addition to all other agreements between the parties, if any, (the Supply Agreement) regarding the subject matter hereof. If there are any direct conflicts between the terms of this Quality Agreement and the Supply Agreement, the following will prevail: Quality AgreementSupply Agreement Amendments to Quality Agreement This Quality Agreement may be amended by the written consent of both parties. The parties agree to amend terms of this Quality Agreement that must be amended in order that the Product continue to meet regulatory requirements of applicable regulatory agencies, as may exist from time to time. If an amendment to this Quality Agreement is proposed, the proposing party will circulate the proposed amendment to the appropriate contact person at Supplier and Client for review and internal approval. The appropriate contact person at Supplier and Client is listed in Appendix 2 (Contacts and Responsibilities). Term of Quality Agreement This Quality Agreement shall commence on the Effective Date and shall remain in effect for as long as the Supplier supplies Product to Client unless the Quality Agreement is terminated earlier in accordance with the terms of this Quality Agreement. Either party may terminate this Quality Agreement upon thirty (30) days written notice to the other party. Use of Third-Parties Supplier shall not allow a third party to manufacture, package, label, inspect, test and release Product unless Supplier has disclosed in writing to Client the Suppliers use of a third party and the Client has provided written approval for the specific third party use. If Supplier employs a third party to perform any or part of the manufacturing, packaging, labelling, inspection, testing, release and/or handling of Product that is supplied to Client, Supplier shall assure that the third party has been fully qualified via the Suppliers third party qualification process prior to performing such activity(ies) unless the Client is providing the qualification of the third party. In this case, the Client will provide the Supplier written qualification documentation. A list of approved subcontractors is contained in Appendix 4. The party employing the subcontractor should have a quality agreement in place consistent with this agreement. Supplier shall have entered into a written confidentiality agreement with any third party providing for confidentiality of all Client information under obligations of confidentiality similar to and requiring the same protection or greater protection of confidential information as the obligations of confidentiality between Supplier and Client. Supplier shall, however, retain all obligations under this Agreement whether or not a third party manufactures, packages, labels, inspects, tests, releases and/or handles Product. If a third party is used by Supplier to manufacture, package, label, inspect, test, release and/or handle Products, Client may, upon request, review the list of such third party(ies) during an on-site visit and/or audit pursuant to the Right To Audit section of this Agreement. Client agrees to treat such information as Confidential Information of Supplier and agrees not to contact any such parties in connection with this Agreement without Suppliers prior consent. Survival Clause All regulatory obligations contained herein that are required of either party or both parties by an applicable regulatory authority shall survive termination of this Quality Agreement. Assignment Supplier shall not assign any or all of its rights or obligations under this Quality Agreement without Clients prior written consent. Clients consent shall not be required in connection with a merger, consolidation, or a sale of all or substantially all of Suppliers assets or the subject matter of this Quality Agreement to another party (an Assignment Transaction). In the event of an Assignment Transaction, Supplier shall provide written notice to Client to the appropriate contact person indicated in Appendix 2 (Contacts and Responsibilities). Client shall have the right to assign any or all of its rights or obligations under this Quality Agreement without the consent of Supplier. In the event of an assignment, the assigning party shall continue to be bound by all pre-existing obligations under this Quality Agreement including all obligations of confidentiality and non-disclosure. Product Specifications Product specifications are listed in Appendix 3. Changes to the agreed upon specifications must be mutually agreed upon and communicated in writing between the parties to this Quality Agreement, except for compendial changes which can be implemented without mutual agreement. Compendial changes must be implemented by the compendial implementation date and communicated between the Supplier and Client. Shipping Under Quarantine Shipping of batches/lots which have not been released. If Client requests the shipment of quarantined or non-conforming material, Client will comply with Supplier's policy by signing a "waiver" attesting that Client is aware of the status of the material and is responsible for controlling its use which includes ensuring the lots/batch under quarantine do not enter into the marketplace until released. Resolution of Quality Issues Quality related disagreements between Supplier and Client that are not resolved in the normal course of business shall be brought to the attention of the appropriate contact person for notices at the Supplier and Client, in writing, as listed in Appendix 2 (Contacts and Responsibilities). If both parties agree that a resolution of the disagreement is reasonably possible, then both Supplier and Client shall agree to work jointly to develop a strategy for such resolution. Supplier and Client further agree to record such resolution in writing. Debarment Supplier warrants and represents that it is not debarred under the Generic Drug Enforcement Act of 1992, 21 U.S.C. 335[a] (the Generic Drug Enforcement Act), and that it has not been convicted of a crime for which it could be debarred under the Generic Drug Enforcement Act. In connection with the Product, the Supplier further warrants and represents, in that it shall not use in any capacity the services of any person debarred under the Generic Drug Enforcement Act, or convicted of a crime for which a person can be debarred under the Generic Drug Enforcement Act. Choice of Law: Jurisdiction/Miscellaneous This Quality Agreement shall be construed and the relationship between the parties determined in accordance with the laws in the State of ______________________, United States of America, without regard to the conflicts of law principals thereof. Any and all disputes between the parties arising out of or related to this Quality Agreement shall be heard in the state and federal courts located in the State of ____________________, and the parties hereby consent and submit to the jurisdiction of such courts. All appendices to this Quality Agreement are attached hereto and incorporated herein by reference. In this Quality Agreement, unless the contrary intention appears: (a) the words "including" and "include" mean "including, but not limited to";(b) the singular includes the plural and vice versa; (c) a reference to a person or entity (including Supplier or Client) includes a reference to the person's executors, administrators, successors, substitutes and assigns; and (d) headings are for reference only and do not form part of this contract. Manufacturing and Testing Location(s) Product will be manufactured and tested at the following location: Address(es): Quality Responsibilities Table ResponsibilitiesNot ApplicableClientSupplier1.Compliance Requirements1.01Implement procedures and/or documented training to meet obligations under this Agreement.oo1.02Follow applicable current Good Manufacturing Practices (cGMPs), including ICH Q7: International Conference on Harmonization Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (API) and locally imposed requirements.o1.03Manufacture, package, ship, store and test the Product and materials in an environment meeting the applicable GMP regulations, which is designed, constructed and maintained in a manner that a) permits the operation therein to be performed under clean, sanitary and orderly conditions; b) permits the effective cleaning of pertinent surfaces; and c) prevents the contamination of the Product and the addition of extraneous material to the Product.oo1.04Manufacture the Product in adherence to applicable regulatory submissions, such as Drug Master File (DMF) if applicable.oo1.05Operate in compliance with applicable environmental, occupational health and safety laws and regulations.oo1.06Maintain a quality unit that is independent of production that fulfils both quality assurance and quality control responsibilities.oo1.07Involve the quality unit in all quality related matters and have them review and approve all quality critical related documents.oo1.08As it relates to this Quality Agreement, notify the other party of name change, corporate reorganization, consolidation, merger or acquisition or sale of the party s company. Notify other party of key personnel changes.o1.09Maintain internal GMP audit program.oo1.10Maintain external GMP audit program for suppliers of raw materials and components, or other suitable qualification program. *Client may qualify a supplier and take this responsibility but must be clearly defined for each materialo*2.Right to Audit2.01Client has the right to audit Supplier s facilities and systems and review documents as they relate to the manufacture of Product. Such inspections and document review shall be conducted by Client at a time, date and duration mutually agreeable to the Supplier and Client and subject to Client signature of a separate confidentiality agreement with the Supplier entity owning the production site.o2.02Client retains the right to conduct reasonable "for cause" audits. Specific goals/scope of the audit, proposed dates and names of the auditors will be agreed upon mutually by the Client and the Supplier.o2.03Issue Supplier a confidential audit report summarizing audit observations.oo2.04Issue responses to all observations documented in the issued audit report in writing to Client Quality Assurance within 30 days of receipt of the report.oo3.Regulatory Inspections and Exchanges3.01Notify Client as soon as the inspection directly involves the Product. Client may be allowed to observe the inspection and contribute input into the discussion. Supplier is responsible for managing the inspection and determining appropriate Client interaction. Notify Client within three business days of the receipt of a Regulatory Authority inspection report, deficiency letter or written regulatory compliance observation, which contains any significant adverse findings that relate to the Product or the facilities used to produce, test or warehouse the Product sold to Client. A significant adverse finding is herein defined as the following: conditions, practices, or processes that adversely affect or may potentially adversely affect product or service quality and/or the rights, safety or well being of subjects/patients and/or the quality and integrity of data, documentation, or other materials or information addressed in the inspection.o3.02As they relate directly to either Product or the facilities used to produce, test, or warehouse, the Product sold to client, Supplier shall provide copies or a summary of the inspection report, deficiency letter or written regulatory compliance observation within 5 business days. These shall be edited to exclude Supplier or other client's proprietary information.oo4.Regulatory Filings and Regulatory Status*4.01Client is responsible for determining the regulatory filing requirements and process. Supplier shall provide information and documentation to facilitate regulatory filings. Financial considerations for this shall be contained within a Supply Agreement.oo4.02(select one approach, if one is not selected then it is Not Applicable) DMF filing/amendments NDA/ANDA CMC filing/changes o o o o o o4.03Responsible for communicating to the other party approvals, deficiencies or rejections by agencies regarding submissions, amendments or updates.o4.04Responsible for submission and maintenance of registrations as follows: Drug substance listing Site establishment registration Or Labeler code as required.  o o o o o o o o o4.05Client shall provide Supplier with the following information regarding the use of the product: Clinical phase of development of the drug product or drug substance that Product is used in and any change regarding this status Intended use of the drug product or drug substance in which that Product is used Regulatory agencies with which the drug product or drug substance is filed and if Product is included in the filing.oo4.06Notify Supplier if Supplier will be named in any governmental filing prior to such filing being made.oo4.07Coordinate the activities necessary to ensure readiness prior to Regulatory Agency Pre-Approval Inspection (PAI).o5.Complaints and Recalls5.01Have written procedures in place to document, investigate, and respond to all quality related complaints.oo5.02Assist in investigations as reasonably requested by Client for complaints associated with Product.oo5.03Retain complaint investigation records and evaluate trends and severity. Implement corrective and preventive actions as necessary.oo5.04Suppliers will have procedures in place to facilitate the recall of an API as necessary. Suppliers will provide assistance to the client for the recall of drug product incorporating the supplier s API.o6.Animal Derived Materials6.01Evaluate and control the risk of Transmissible Spongiform Encephalopathy (TSE) for raw materials and components. Maintain appropriate records for each lot of animal derived material to ensure traceability. Where required by local regulations, Supplier will assure that the country of origin or slaughtering information (either or both, which ever can be obtained from the manufacturer) will be documented and provided to Client.o 7.Validation/Qualification7.01Determine according to Product lifecycle and guidance documents when process validation is required.oo7.02Have a written master validation/qualification plan for the facilities, equipment/instruments, manufacturing process, cleaning procedures, analytical procedures, in process control tests and computerized systems as appropriate. These to be approved by the quality unit. Client may provide validated methods, process validation, and in-process controls. Written copies to be provided to Supplier.o7.03Responsible for developing, preparing and maintaining validation documentation approved by the quality unit, including protocols, reports and associated documentation. oo7.04Qualify as necessary all critical systems and equipment used for the manufacture and control of Product (Installation Qualification (IQ), Operational Qualification (OQ), and/or Performance Qualification (PQ)).oo7.05Allow viewing of the validation documentation for the Product during an onsite audit.oo 8.Documentation and Records8.01Have a controlled system to initiate, review, revise, approve, obsolete and archive all Good Manufacturing Practices documentation. At a minimum, all production, control, and distribution records should be retained for at least 1 year after the expiry date of the batch. For APIs with retest dates, records should be retained for at least 3 years after the batch is completely distributed.oo8.02Supplier shall generate the master batch production record, labeling and packaging procedures for the manufacture of the Product based on the information supplied by Client. Both parties may approve the master batch production record. Any changes to the master batch production record, labeling and packaging procedures for the manufacture of the Product shall go through Supplier change control system and may be approved by Client. Suppliers change control system will include maintenance of a revision history file and justification for changes initiated by both parties. Client shall provide justification for changes initiated by Client.o8.03Maintain a document control system for specifications and test methods, including: raw materials, Product labeling, packaging materials and other materials that would likely affect product quality.oo8.04Will provide the following document for lot/batch produced: Complete Certificate of Analysis for the Product, containing "at minimum" the following information: Supplier Product number Supplier lot/batch number Name of Product Name of the test Specification limit Expiration or retest date, if applicable Test result (as a numerical value, unless designated Pass/Fail in the specification limit, statistical values can be used if data supports their use except for assays and impurity tests), including retest results if required Quality Assurance approval and date. Manufacturing Site (name and address) Manufacturing Date Requested copies of: Batch Records o Significant Deviations o Analytical Data o Certificate of Origin o Certificate of Compliance o Others& o oo8.05Where applicable, electronic signatures used on the certificate of analysis or other controlled documents should be authenticated and secure.oo9.Annual Product Reviews9.01Have procedures to conduct and document annual product reviews, if applicable.oo9.02Allow viewing of the Annual Product Review (APR) for the Product during an on-site audit. Client approval is optional.oo10.Change Control10.01Have established written procedures for control of changes impacting the Product including manufacturing components or process, computer hardware/software, Product specifications, test methods, vendors, and subcontractors, if applicable. 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t644 laytah @Dr$$$$ p@ @@@@$Ifa$gdahoK$$$$$ p@ @@@@$Ifa$gdahK$Ukd4$IfK$L$l0 t644 laytahDFrvr$$$$ p@ @@@@$Ifa$gdahoK$$$$$ p@ @@@@$Ifa$gdahK$Ukd$IfK$L$l0 t644 laytahvxr$$$$ p@ @@@@$Ifa$gdahoK$$$$$ p@ @@@@$Ifa$gdahK$Ukd$IfK$L$l0 t644 laytah‡ćȇuW$$$$ p@ @@@@$Ifa$gdahoK$$$$$ p@ @@@@$Ifa$gdahK$$$$ p@ @@@@$IfgdahoK$Ukdo$IfK$L$l0 t644 laytahȇʇ̇·Ї|||$$$$ p@ @@@@$Ifa$gdahK$jkd؏$IfK$L$l4F`` t6    44 laytahЇ҇ԇև؇|||$$$$ p@ @@@@$Ifa$gdahK$jkdl$IfK$L$l4F   t6    44 laytah؇ڇ܇~uuu $$Ifa$$$ p@ @@@$If^a$gdvI6jkd$IfK$L$l4F   t6    44 laytah"$(*^`dfp & "$(*.0VX\^jHԍ؍ڍ܍ލϸڸڳӸڸڪڸڸڳڡښڸ hDl5CJh<hvI6CJhL^hvI6CJ hvI65,hjhvI6OJPJQJ^JmH nH sH tH hvI6 hvI65CJ hvI6CJ,hYhvI6OJPJQJ^JmH nH sH tH hvI65CJ\<B9'9$$ p@ @@@@$Ifa$ $$Ifa$kd$$IfTs4    r!%0    62 4 saf4yt:T 9. $$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$Ifa$ "$&(*0^`bdfp$$ $Ifa$Ff  & F $If $$$Ifa$gd=BFf! $$$Ifa$$$If&B3+$$If$$ $Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T"$7kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$$&(*,.08VXZ\^jڍލ $$Ifgd Ff & F $If^ $$$Ifa$gdDlFf$$If $$$Ifa$lnprtvxzLNPRTVXZ^`df  " ".TVʜ̜Μh<hvI6B*CJph hvI65hvI6,hYhDlOJPJQJ^JmH nH sH tH ,hjhDlOJPJQJ^JmH nH sH tH U hvI65CJ hvI6CJhvI65CJ\@B7/77$$If $$$Ifa$kd|$$IfTs4    r!%0    62 4 saf4ytvI6T and gain approval from Client within a reasonable time of intent to make changes that could impact the identity, strength, safety, potency, stability, purity, or regulatory status prior to implementation of the change (called significant*).o10.03Issue to Client a written evaluation of the significant* change including change justification so that Client can determine the impact of use of Product in Client s finished product.oo10.04Jointly establish a strategy to secure regulatory approvals for significant changes, as necessary.o11.Deviations11.01Have procedures for the identification, investigation, and reporting of deviations and Out-of-Specification (OOS) results that occur during the manufacture and testing of the Product.oo11.02Document and explain all deviations. Investigate OOS results and critical deviations. Extend the investigation to other lots that may have been associated with the failure as appropriate. Include preventive actions and track these to completion.oo11.03Evaluate deviations to determine impact on validation/qualification studies.11.04Notify Client of significant deviations within 3 business daysoo12.Reprocess and Batch Adjustments /Rework/Retest12.01Have procedures for batch adjustments and reprocessing, if applicable. Reprocessing is defined as introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g. distillation, filtration, chromatography, and milling) that are part of the manufacturing process.oo12.02Will not blend Out of Specification batches with other batches for the purpose of meeting specifications.oo12.03Have a protocol for Product requiring rework describing the rationale and justification for rework for approved filed rework processes, if applicable. Rework is defined as subjecting an intermediate or API that does not conform to standards or specifications to one or more processing steps that are different from the established manufacturing process to obtain an acceptable quality intermediate or API (e.g. recrystallizing with a different solvent).oo12.04Receive written approval by Client for reprocessing and reworking outside of approved filed processes.oo12.05Will not perform recovery of materials and/or solvents unless approved procedures and specifications are in place.oo13.Production and In Process Controls, Packaging and Labeling13.01Procure, test as required, and release raw materials and packaging and labeling materials used in manufacture of Product. Client approval is optional.oo13.02Establish and document specifications for raw materials, Product labelling and packaging materials and other materials that would likely affect product quality. Client approval is optional.oo13.03Prepare/develop master batch production records in accordance with applicable cGMP requirements or guidelines, as applicable for lifecycle of product. Client approval is optional.oo13.04Inspect, weigh and measure raw materials used for Product manufacturing and verify critical weighing by a second individual or validated automated system.oo13.05Manufacture Product in a manner that prevents contamination by other materials including carryovers.oo13.06Provide product label to include: name and address of the manufacturer, identifying code, batch number, quantity of contents, storage and special transport conditions if applicable, the retest or expiry date and any special requirements. Revise label per change control as necessary.oo13.07Review and approval of batch production records by quality unit prior to batch release.oo13.08Release Product by quality unit. Client release is an option.oo14.Storage and Distribution14.01Maintain storage facilities appropriate for conditions specified on the Product label. Maintain records of any critical storage conditions.o14.02Have systems for controlling quarantined, rejected or recalled materials.oo14.03Provide Material Safety Data Sheets or equivalent. (select one)ooo14.04Notify client in a timely manner if Supplier lp7/$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$ptxz7kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$LPTX $$$Ifa$$$$ p@ @@@@$Ifa$XZ\^`bB6-66 $$$If $$$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6Tbdfn  $$$IfFf & F $If^$$$$Ifa$gdDlFf! $$$$Ifa$ "B6-66 $$$If $$$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T ".Ȝʜ6- $$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$ʜΜҜԜ^6- $$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$ΜМҜԜ^`bdfhjlprvxޝ=w  ڼڼڷӳڼڼڼڥh<5CJ\,hjh<OJPJQJ^JmH nH sH tH  h<CJ h<5CJ h<hvI6hvI6 hvI65,hjhDlOJPJQJ^JmH nH sH tH  hvI65CJ hvI6CJhvI65CJ\,hYhDlOJPJQJ^JmH nH sH tH /^bfjl6kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$lnprtvxޝ $$$ p@ @@@@$Ifa$Ff & F $If^ $$$Ifa$gdDlFf-$$If $$$Ifa$ B7/77$$If $$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6TK7/$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$ 7/$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$  §ħƧȧʧ̧ΧЧܧXZ\^`bdڼڼڼڬڼڼڼh<57CJ\ h<5h< hvI65 hvI65\ hvI6CJ hvI65CJhvI65CJ\ h<7CJ,hjh<OJPJQJ^JmH nH sH tH  h<5CJ h<CJh<5CJ\,hYh<OJPJQJ^JmH nH sH tH 27kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$/kdĽ$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$$$If §ƧʧΧ$$$ p@ @@@@$Ifa$Ff & F $Ifgd< $$$Ifa$gd<FfE$$If $$$Ifa$ΧЧܧX\`B7/77$$If $$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T`dfrڪު7/$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$dfrڪܪު*,.02468D(bdfhjlnp|,.02468:FİưȰʰ̰ΰаҰְذܰްһܲܲܲܲܲhvI65CJ\ hvI6CJ hvI65CJh<5CJ\,hYh<OJPJQJ^JmH nH sH tH h<57CJ\,hjh<OJPJQJ^JmH nH sH tH  h<5CJ h<CJ;ު*7/$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$*.268D7kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$D/kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$$$If(bfjn$$If $$$Ifa$np|,04B7/77$$If $$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T48:FİȰ7/$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$Ȱ̰аҰ԰7+ $$$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$Ifa$԰ְذڰܰް ,DHLPFf & F $If^$$$$Ifa$gd<Ff $$$$Ifa$ $$$Ifް ,BDFHJLNPR^ lnprtvxz|~ͩͩͯ͠ hvI65\U,hjhMUOJPJQJ^JmH nH sH tH h<5CJ\ h<CJ h<5CJ,hYh<OJPJQJ^JmH nH sH tH ,hjh<OJPJQJ^JmH nH sH tH  hvI65CJhvI65CJ\ hvI6CJ hvI652PR^B6-66 $$$If $$$$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T 6- $$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$l6- $$$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$finds a quality issue post Supplier release/shipment.oo15.Laboratory Controls15.01Have written procedures for sample management, testing, approval, disposition, recording, storage, retention and disposal of laboratory data.oo15.02Retain samples as required by regulatory agencies.oo15.03Have written procedures and appropriately document the preparation, use and management of reagents, solutions, and standards.oo15.04Have appropriate specifications and test procedures for the Product which are consistent with the applicable approved filing and/or compendial monograph.o15.05Test Product in accordance with approved validated or qualified methods and specifications using calibrated equipment.oo15.06Have a program for qualification, calibration, and preventive maintenance of all analytical equipment.oo15.07Responsible for analytical method development, qualification and or validation as appropriate. If provided by the Client, Client will provide written copies to the Supplier.o15.08Responsible for transferring any developed methods to Supplier.oo15.09If commercially available reference standards are not available, reference standards for the Product will be provided.oo16.Stability (must decide Client or Supplier or NA)* if supplied by Client, Client will provide all necessary information to the supplier.16.01Maintain a documented, ongoing stability program to monitor the stability of the Product using stability indicating procedures. ooo16.02Data analysis and trending reporting will be performed.ooo16.03OOS notification to other party will be provided in a timely manner.ooo16.04Use data to confirm appropriateness of storage conditions and retest or expiry date.ooolptxz|6- $$Ifa$kd $$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$|~$$ p@ @@@@$Ifa$Ff & F $If^ $$Ifa$gdMUFf $$Ifa$$Iffhjlnprt|~˴ݗԮݮݗԮݮݗԮдݗԮݮݗ,hYhMUOJPJQJ^JmH nH sH tH  hMUCJ,hjhMUOJPJQJ^JmH nH sH tH  hMU5hMUhMU5CJ\ hMU5CJhvI65CJ\ hvI65CJ hvI6CJ hvI65;fjnB9399$If $$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6Tnrt|93$Ifkd$$IfTs4    r!%0    62 4 saf4ytvI6T $$Ifa$93$Ifkd $$IfTs4    r!%0    62 4 saf4ytvI6T $$Ifa$9kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$Ifa$ $$Ifa$$$ p@ @@@@$Ifa$B9399$If $$Ifa$kd$$$IfTs4    r!%0    62 4 saf4ytvI6T29.&$$If $$$Ifa$kd0$$IfTs4    r!%0    62 4 saf4ytvI6T $$Ifa$2468:<>@LXr궭ͭꖭ䏊~u~hvI65CJaJhlhvI65CJaJ hvI65 hvI65\,hjh6OJPJQJ^JmH nH sH tH hvI65CJ\,hYhMUOJPJQJ^JmH nH sH tH ,hjhMUOJPJQJ^JmH nH sH tH  hvI6CJ hvI65CJ hMUCJhMU5CJ\.26:>@L $$$$Ifa$ $$$If $$Ifa$FfFf1$$IfFf $$$Ifa$  $$$If $$Ifa$Ff $$$$Ifa$ & F $If^gd6 $$Ifa$gdMUFf   .02468:<FH, , ,,,,,,,,,,,,l.n.p.r.t.v.x.z.|.~...........ӻ hvI65 hvI65\hvI6U hH-"CJ hvI65CJ,hjhH-"OJPJQJ^JmH nH sH tH hvI65CJ\ hvI6CJJ B90$ $$$$Ifa$ $$$If $$Ifa$kdn$$IfTs4    r!%0    62 4 saf4ytvI6T6- $$Ifa$kdz$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$.26: $$$$Ifa$ $$$IfgdH-":<HB90$ $$$$Ifa$ $$$If $$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T ,6- $$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$16.05Store stability samples in commercial size and/or simulated market containers under ICH storage conditions.ooo16.06Place the first three commercial production batches and at least one batch per year (if a batch is produced in the year) on stability or as required by applicable regulatory agencies.ooo17.Recalls17.01In the event that either Client or Supplier determines that an event or circumstance has occurred relating to the manufacture or stability of the Product which may result in the need for a recall, stock recovery ormarket withdrawal of Client's finished drug product, Supplier and Client shall consult with each other in a timely manner. The final decision to recall any of the Client's drug products shall be made by Client.o17.02Notification of the recall or similar action to the authorities, distributors and customers of the finished drug product shall be made by Clientoo APPENDIX 1: Definition of Product  Product shall mean the following Products: ,,,,,,-kd$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$ $$$If,,n.r.v.z. $$$$Ifa$$$$$ p@ @@@@$Ifa$ $$Ifa$z.|.~..B9$$$$$ p@ @@@@$Ifa$ $$Ifa$kd$$IfTs4    r!%0    62 4 saf4ytvI6T.....6kd$$IfTs4    pr!%0    62 4 saf4ytvI6T $$$$Ifa$........122 2$$$$ p@ @@@@$Ifa$ $$Ifa$Ff= $$$$Ifa$  & F $If $$Ifa$gdH-" ..22222 2 222<3>3@3B3D3F3H3J33334HNHOHPHkHHHH׉ׅ}{rlg^W hw5CJhw6CJaJ hw5 hwCJhw5CJ\UhDnh&Gkhw,hYh6OJPJQJ^JmH nH sH tH ,hjh6OJPJQJ^JmH nH sH tH hvI65CJ\,hYhH-"OJPJQJ^JmH nH sH tH  hvI6CJ,hjhH-"OJPJQJ^JmH nH sH tH hvI6 hvI65CJ 222<3B9$$$$$ p@ @@@@$Ifa$ $$Ifa$kd,$$IfTs4    r!%0    62 4 saf4ytvI6T<3@3D3H3J3361gddkd8$$IfTs4    r!%0    62 4 saf4ytvI6T $$$$Ifa$3333333334HHHHHHHH H H H H HHHHHHHH APPENDIX 2: Contacts and Responsibilities Contact Person for Notices (including Notices of Amendment, Assignment,Termination, Resolution of Quality Issues)SupplierClientName:Title:Phone/Fax:Address (mail/delivery):E-mail Address:With a Copy to:Name:Title:Phone/Fax:Address (mail/delivery):E-mail Address: APPENDIX 3: Product Specifications APPENDIX 4: List of Approved Subcontractors     Page  PAGE 2 of  NUMPAGES 21 Business Confidential HHHHHHHHHHHH H!H"HNHOHPHkHH $$Ifa$$a$gddHHHv$$$ !h$If^ha$skdD$$Ifl4#"  04 la.f4p HHHHHHHHHHHHHHHHHHHHHIIIIIII I!I#I$I%I&I'I(I8I9I:I;II?IOIQIRISIUIVI\I^I_I`IbIcIjIlImInIpIqI|I~IIIIIIIIIIIIIIIhwCJ\aJmHnHuhw56CJaJhwCJaJ hw5hw hwCJhw5>*CJ\aJLHHHHHmm$$$ !h$If^ha$ $$Ifa$skd$$Ifl4p#"  04 la.f4p HHHHHPJ77$$ !H$If^H$Ifkd$$Ifl4F # \  0    4 la.f4pHHHHHRI66$$ !H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4pHHHHHRI88$$ H$If^H $$Ifa$kd$$Ifl4F # \  0    4 la.f4pHHHHHRI88$$ H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4pHHHHHRI88$$ H$If^H $$Ifa$kd $$Ifl4F # \  0    4 la.f4pHHIIIRI88$$ H$If^H $$Ifa$kd $$Ifl4F # \ 0    4 la.f4pIIIIIRI88$$ H$If^H $$Ifa$kd" $$Ifl4F # \  0    4 la.f4pII!I"I#IRI88$$ H$If^H $$Ifa$kd< $$Ifl4F # \ 0    4 la.f4p#I$I%I&I'IRI?.$$ H$If^H H$If^H $$Ifa$kdH$$Ifl4F # \  0    4 la.f4p'I(I8I9I:IRI?.$$ H$If^H H$If^H $$Ifa$kdb$$Ifl4F # \ 0    4 la.f4p:I;IIRI66$$ !H$If^H $$Ifa$kdn$$Ifl4F # \  0    4 la.f4p>I?IOIPIQIRI66$$ !H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4pQIRISITIUIRI66$$ !H$If^H $$Ifa$kd$$Ifl4F # \  0    4 la.f4pUIVI\I]I^I]TAA$$ !H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4p^I_I`IaIbI]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \  0    4 la.f4pbIcIjIkIlI]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4plImInIoIpI]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \  0    4 la.f4ppIqI|I}I~I]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4p~IIIII]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \  0    4 la.f4pIIIII]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4pIIIII]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \  0    4 la.f4pIIIII]TCC$$ H$If^H $$Ifa$kd$$Ifl4F # \ 0    4 la.f4pIIII J J J J]TOOTTF$a$gdd$a$kd$$Ifl4F # \ 0    4 la.f4pIIJJ J JJJJJJJJJJJ%J&J'J(J,J-J8J9J;J*CJaJmH sH tH V`"V 0b] Heading 2$xx@&a$5>*aJmH sH tH h@2h  Heading 3+$ & F p@ @@@@xx@&a$aJmH sH tH h@Bh  Heading 4+$ & F p@ @@@@xx@&a$aJmH sH tH 8@A8  Heading 5  & F@&p@p  Heading 6+$ & F p@ @@@@<@&a$6CJaJmH sH tH t@t  Heading 7+$ & F p@ @@@@<@&a$CJOJQJaJmH sH tH x@x  Heading 8+$ & F p@ @@@@<@&a$6CJOJQJaJmH sH tH z @z  Heading 9+ $ & F p@ @@@@<@&a$"56CJOJQJaJmH sH tH DA@D Default Paragraph FontVi@V  Table Normal :V 44 la (k(No List TOT Heading Char Char5>*CJOJPJQJaJHOH Char Char12CJOJPJQJ^JaJHOH Char Char11CJOJPJQJ^JaJHO!H Char Char10CJOJPJQJ^JaJFO1F Char Char9CJOJPJQJ^JaJFOAF Char Char86OJPJQJ^JaJFOQF Char Char7CJOJPJQJ^JaJJOaJ Char Char66CJOJPJQJ^JaJLOqL Char Char556CJOJPJQJ^JaJpS@p Body Text Indent 3!$ p@ @@@@h^ha$aJmH sH tH FF  Char Char4CJOJPJQJ^JaJDOD List Paragraph ^m$HC@H Body Text Indenthx^hROR Char Char3$CJOJPJQJ^JaJmH sH tH Z@Z pTOC 1&$ $0*H@ 0^`0a$aJmH sH tH L@L Header$ !@a$aJmH sH tH >>  Char Char2CJOJPJQJ4 @4 Footer H$NON Char Char1 CJOJPJQJaJmH sH tH .)@!. 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